Well, okay, I think we're ready for a bit of a transition now to talk about stages of sleep, and how they can be recognized clinically, and how they can be monitored. So before I can describe in detail for you the stages of sleep, we need to have a bit of a primer on electroencephalography. Which is a means of recording this ongoing activity of the human brain, which we sometimes call brain waves. Well, I had opportunity to think about brain waves fairly recently, as I had a very quick. vacation away from recording these videos with you all and got to go to one of my favorite places on the planet and enjoy a cool but beautiful day by the ocean watching waves and thinking about waves in the brain. So I can't help but to watch waves on the ocean. And think of waves of activity in the brain and wonder how turbulent are the seas of electrical activity at the moment, going on in, in my brain, perhaps yours as well. And looking at the ocean is a just a. [NOISE] Intriguing reminder of the rhythms in nature and those rhythms are present in the patterns of activity we have in our brain. Sometimes we forget that, we consider what's going on in our brain as being totally driven by what we're seeing or what we're. Hearing or what we're saying but, in reality, our brain is carrying out it's own rhythms, very much like these waves before me. >> Well I always feel invigorated when I visit that spot, and so with Some of those images in mind. let's move on and talk about waves in the brain, and how we can measure them. So the electrical activity in the cerebral cortex, of course, is ongoing. And it reflects the integrated functions of, really tens of billions of neurons across the cerebral hemispheres and this activity can generate macroscopic currents that are flowing through the tissues. And these electrical currents can be recorded from the scalp on the external surface of the head. And this is the basis of this technology called electroencephalography which is what we see here, so the scientists and clinicians have standardized the numbers and placements of the electrodes on the scalp that allow for systematic sampling of the cerebral mantle as it's present on the superficial aspects of the brain. So what we're looking at here is the placement of these electrodes as they are done in a standard experimental or clinical environment. So, here's an illustration that attempts to provide a bit of the principle involved here. So, imagine that a neuron is receiving input from some source, and as these neurons, receive that input. They're depolarized and ions are flowing across the plasma membrane, and for excitatory post synaptic potentials, that means positive charge is entering the post synaptic process. So as that Positive charges entering the cell, that's essentially an inward current. So that is a current sync. There is a negativity at that site, where there is this, aggregate of active synapses. So positive charge is going to flow through the extracellular fluids. Towards that current sink. So where that current is coming from then, is going to become the source of current. And so, there are these sinks and sources, these current dipoles that are in register [SOUND] throughout the cortical mantle because of the organization of these pyramidal cells. So wherever these pyramidal cells are oriented perpendicularly to the surface of the skull we have the potential to be able to record these electrical dipoles with a placement of an electrode close to the surface of the brain. Now obviously as the, solsi of the cerebral mantle fold in upon itself its going to be very difficult to record dipoles that are buried in the depth of the sulkus. So electroencephalography really is limited to these more superficial dipoles that are present on the crests of the gyri of the cerebral hemispheres. [SOUND]. Well, what we actually record, then, reflects the aggregate activity of these neurons. And so, at any one location, we're going to have. The active inputs that are engaged in some kind of pattern of neural activity. Whether we actually see that at the surface of the scalp is going to depend upon a variety of factors, mainly the number of active neurons that underlie the scalp electrode. The firing rate of those active neurons and most importantly the synchrony of the active population. So here for example we see a a cluster of neurons receiving inputs, and when these inputs are firing in an, in a regular fashion we find that each one neuron might be generating electrical signals that when attenuated in time have the form of these various waves, and the algebraic sum of those waves, which is what would be seen with the scalp electrode, is a low-amplitude but higher frequency kind of pattern. So this is consistent with an irregular pattern of activity at the level of inputs to a population of neurons. This is actually consistent with the transfer of information and the processing of signals that might be going on within a cortical column. Now, on the other hand, if it were possible to synchronize the inputs to this population of cells, we may find that many neurons are essentially engaged in firing at more or less the same time. And these signals might then sum algebraically and produce a much more noticeable wave in the electroencephalographic recording from the surface. So when there is synchronous input activity to a local region of the cerebral cortex, we tend to have higher amplitude. But lower frequency oscillations that can be recorded. And as we'll see the synchronized pattern of activity is indicative of non-rem sleep. Well there is another context in which one can see highly synchronous activity and it's not good. Highly synchronous electroencephalographic activity can be the hallmark of a seizure. So, this is a representation of electroencephalographic data from an individual that, experienced a seizure. So here we see a healthy looking. high frequency, low amplitude activity recorded between pairs of scalp electrodes. And then with the onset of the seizure, we see this massive synchronous discharge, as indicated by these high amplitude, lower frequency waves That emerge in this patient, synchronously, across the entire brain. So this would be an example of what we call a generalized seizure, because it involves almost the entire brain all at once. So this pattern of brain activity would be considered to be pathological. So, putting that aside for the moment. Normal patterns of electroencephalographic activity generally fall into four recognized frequency bands. beginning with the lowest frequency bands we can see healthy brain oscillating. And very large amplitude, very slow waves in what's called the Delta band, this is one to four cycles per second, one to four hertz. This as we'll see is indicative of the deepest stage of sleep. The next highest band of activity that is recognized is called the theta band and this is a rhythm between 4 and 7 hertz. Theta activity is consistent with being awake and perhaps being engaged in some sort of active exploration of your surroundings. Next we have the alpha band, the alpha rhythms. Alpha is between 8 and about 13 hertz. And the alpha rhythms seem to be a prominent feature of our sensory cortical areas, especially when those cortical areas are. Somewhat disengaged from the sensory environment. So, if for example, if one were to close ones eyes. You'd find that the visual cortex very quickly will go into a alpha rhythm. With large amplitude waves in this eight to 13 or so hertz range. And when we open our eyes for most people anyway the alpha rhythm will go away just about immediately, so the alpha rhyme is an indication that a sensory cortex is in a state of quiet rest. Now the highest frequency waves that we typically recognize are in the, beta range sometimes we split this into beta and gamma with, beta being anything above 12 hertz basically. And gamma being around 40 to 60 hertz. So gamma waves beta waves these are high frequency but very low amplitude waves. So this would be indicative of a high degree of. irregular activity or high degree of desynchronization within cortical networks, and this might be consistent with the [UNKNOWN] granular processing of information that is happening at the Culumnar or perhaps the modular level... within our cortical networks. So electroencephalographic recording is very important from a clinical perspective. It can be used to diagnose disorders like epilepsy or seizure disorder and it can be used to investigate various stages of consciousness, including the normal transitions from sleep to wakefulness and then back to sleep again. As well as, brain states that are associated with injury to the brain itself. Including coma and minimally conscious states of activity. So let's now see how electroencephalographic data can be used to categorize the various stages of sleep. Well, the electroencephalogram has provided psychiatrists and other kinds of physicians who study sleep the opportunity to characterize the progression of an individual from being fully awake to being deeply asleep, and we use these electroencephalogramic criteria to recognize essentially. Five stages of sleep. Four stages of non-REM sleep, and then we can recognize REM sleep, based on the behavior of the individual and the electroencephalographic record. So stage one sleep is a time when we are beginning to feel drowsy. we are otherwise still awake but beginning to experience that transition from being vigilant to being quite drowsy. So during stage one sleep, we begin to see the emergence of some higher amplitude rhythms. Still fairly fast and the increase in amplitude only modest, but it's consistent with The increase in synchronicity that is going to lead to more deeper stages of sleep. So, in stage two sleep, then, this is the next deeper stage. We see an increase in amplitude. And then we see the emergence of a very particular feature that is characteristic of this stage of sleep. It's called the sleep spindle. And this sleep spindle is a very brief, just a few seconds of high-frequency activity that occurs in these clusters. So it's a high-amplitude, high-frequency burst that is indicative of There being a great deal of synchrony imposed upon thalamocortical neurons but only for these little brief epochs of time. And so this is something that's happening as we begin to enter our deeper stages of sleep. So stage two sleep might pass after 15 or 20 minutes or so and we begin to get into a stage of sleep that, more clearly is increasing the amplitude of some of these brain waves. So the electroencephalogram evidence is suggesting that the brain is, getting even more hypo synchronous but that the rhythms are also slowing. So with stage three sleep we're getting into fairly moderate levels of sleep. The sleep spindles have gone away now and the electroencephalogram is characterized by the emergence of these larger amplitude waves, but we see the deepest stage of sleep. In state four, and this is when the electroencephalogram reveals large amplitudes, slow delta waves, and these waves are indicative of a cerebral cortex that is dissociated from its environment and is engaged in this hyper synchronism slow rhythm of thalamocortical oscillation. Now, once we cycle down to stage 4, to deep sleep, after some period of time, maybe an hour, an hour and a half or so, something fairly dramatic happens. We begin to step out of that deep slow wave sleep, and we enter a stage of sleep Where the electroencephalogram reverts to a low-amplitude, high-frequency pattern, something that resembles actually what the electroencephalogram looks like in the awake state. This is called REM sleep. REM stands for rapid eye movement sleep. It's also called paradoxical sleep. And the paradox is, how can we be still asleep and yet have electroencephalographic activity that resembles an awake brain.